Altered M1/M2 activation patterns of monocytes in severe relapsing experimental rat model of multiple sclerosis. Amelioration of clinical status by M2 activated monocyte administration
Abstract
Objectives:We investigated proinflammatory M1 and immunomodulatory M2 activation profiles of circulating monocytes in relapsing experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis, and tested whether altered M1/M2 equilibrium promotes CNS inflammation. Results:Approaches of MRI macrophage tracking with USPIO nanoparticles and expression patterns of M1/M2 macrophages and microglia in brain and M1/M2 monocytes in blood samples at various disease stages revealed that M1/M2 equilibrium in blood and CNS favors mild EAE, while imbalance towards M1 promotes relapsing EAE. We consequently investigated whether M2 activated monocyte restoration in peripheral blood could cure acute clinical EAE disease. Administration of ex vivo activated M2 monocytes both suppressed ongoing severe EAE and increased immunomodulatory expression pattern in lesions, confirming their role in the induction of recovery. Conclusion:We conclude that imbalance of monocyte activation profiles and impaired M2 expression, are key factors in development of relapses. Our study opens new perspectives for therapeutic applications in MS.
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A switch from M1- to M2-associated gene expression has been reported during cutaneous wound healing but has not been observed in studies of immune-mediated and toxin (cuprizone)-induced demyelination.
“A switch from M1- to M2-associated gene expression has been reported during cutaneous wound healing8 but has not been observed in studies of immune-mediated36 and toxin (cuprizone)-induced demyelination37.”
From M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination (2013) · cites this paper as [36]
Cites
Exploring the full spectrum of macrophage activation
Mosser, D. M., & Edwards, J. P. (2008) · Nature Reviews Immunology · doi:10.1038/nri2448 · Cited by 9,144 · see citing works
The chemokine system in diverse forms of macrophage activation and polarization
MANTOVANI, A., SICA, A., SOZZANI, S., ALLAVENA, P., VECCHI, A., & LOCATI, M. (2004) · Trends in Immunology · doi:10.1016/j.it.2004.09.015 · Cited by 6,534 · see citing works
Alternative activation of macrophages
Gordon, S. (2003) · Nature Reviews Immunology · doi:10.1038/nri978 · Cited by 6,189 · see citing works
Obesity induces a phenotypic switch in adipose tissue macrophage polarization
Lumeng, C. N., Bodzin, J. L., & Saltiel, A. R. (2007) · Journal of Clinical Investigation · doi:10.1172/jci29881 · Cited by 4,664 · see citing works
Type II monocytes modulate T cell–mediated central nervous system autoimmune disease
Weber, M. S., Prod'homme, T., Youssef, S., Dunn, S. E., Rundle, C. D., Lee, L., Patarroyo, J. C., Stüve, O., Sobel, R. A., Steinman, L., et al. (2007) · Nature Medicine · doi:10.1038/nm1620 · Cited by 447 · see citing works
Alternative activation of macrophages: immune function and cellular biology
Varin, A., & Gordon, S. (2009) · Immunobiology · doi:10.1016/j.imbio.2008.11.009 · Cited by 361 · see citing works
Myelin-laden macrophages are anti-inflammatory, consistent with foam cells in multiple sclerosis
Boven, L. A., Van Meurs, M., Van Zwam, M., Wierenga-Wolf, A., Hintzen, R. Q., Boot, R. G., Aerts, J. M., Amor, S., Nieuwenhuis, E. E., & Laman, J. D. (2006) · Brain · doi:10.1093/brain/awh707 · Cited by 353 · see citing works
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M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination
Miron, V. E., Boyd, A., Zhao, J.-W., Yuen, T. J., Ruckh, J. M., Shadrach, J. L., van Wijngaarden, P., Wagers, A. J., Williams, A., Franklin, R. J. M., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3469 · Cited by 1,788 · see citing works
Microglia and brain macrophages in the molecular age: from origin to neuropsychiatric disease
Prinz, M., & Priller, J. (2014) · Nature Reviews Neuroscience · doi:10.1038/nrn3722 · Cited by 1,329 · see citing works
Obesity in autoimmune diseases: Not a passive bystander
Versini, M., Jeandel, P.-Y., Rosenthal, E., & Shoenfeld, Y. (2014) · Autoimmunity Reviews · doi:10.1016/j.autrev.2014.07.001 · Cited by 694 · see citing works
IL-4 in the brain: a cytokine to remember
Gadani, S. P., Cronk, J. C., Norris, G. T., & Kipnis, J. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1202246 · Cited by 549 · see citing works
Microglia/Macrophage Polarization Dynamics in White Matter after Traumatic Brain Injury
Wang, G., Zhang, J., Hu, X., Zhang, L., Mao, L., Jiang, X., Liou, A. K.-F., Leak, R. K., Gao, Y., & Chen, J. (2013) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2013.146 · Cited by 473 · see citing works
Diversity and plasticity of microglial cells in psychiatric and neurological disorders
Nakagawa, Y., & Chiba, K. (2015) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2015.06.010 · Cited by 208 · see citing works
The benefits and detriments of macrophages/microglia in models of multiple sclerosis
Rawji, K. S., & Yong, V. W. (2013) · Clinical and Developmental Immunology · doi:10.1155/2013/948976 · Cited by 217 · see citing works
“In this regard, the transfer of M2-polarized monocytes resulted in a suppression of EAE [53, 54].”
BackgroundRole of microglial m1/m2 polarization in relapse and remission of psychiatric disorders and diseases
Nakagawa, Y., & Chiba, K. (2014) · Pharmaceuticals · doi:10.3390/ph7121028 · Cited by 215 · see citing works
Functional diversity of microglia – how heterogeneous are they to begin with?
Hanisch, U.-K. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00065 · Cited by 195 · see citing works
P2X4 receptor controls microglia activation and favors remyelination in autoimmune encephalitis
Zabala, A., Vazquez‐Villoldo, N., Rissiek, B., Gejo, J., Martin, A., Palomino, A., Perez‐Samartín, A., Pulagam, K. R., Lukowiak, M., Capetillo‐Zarate, E., et al. (2018) · EMBO Molecular Medicine · doi:10.15252/emmm.201708743 · Cited by 192 · see citing works
Peferoen, L. A. N., Vogel, D. Y. S., Ummenthum, K., Breur, M., Heijnen, P. D. A. M., Gerritsen, W. H., Peferoen-Baert, R. M. B., van der Valk, P., Dijkstra, C. D., & Amor, S. (2015) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0000000000000149 · Cited by 178 · see citing works
Csf1R inhibition attenuates experimental autoimmune encephalomyelitis and promotes recovery
Nissen, J. C., Thompson, K. K., West, B. L., & Tsirka, S. E. (2018) · Experimental Neurology · doi:10.1016/j.expneurol.2018.05.021 · Cited by 168 · see citing works
Loss of IL-10 Promotes Differentiation of Microglia to a M1 Phenotype
Laffer, B., Bauer, D., Wasmuth, S., Busch, M., Jalilvand, T. V., Thanos, S., Meyer zu Hörste, G., Loser, K., Langmann, T., Heiligenhaus, A., et al. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00430 · Cited by 120 · see citing works
Vereyken, E. J., Heijnen, P. D., Baron, W., de Vries, E. H., Dijkstra, C. D., & Teunissen, C. E. (2011) · Journal of Neuroinflammation · doi:10.1186/1742-2094-8-58 · Cited by 108 · see citing works
“Administration of AA macrophages reduced the development of relapses during the relapsing EAE model [82].”
BackgroundMaternal immune activation leads to activated inflammatory macrophages in offspring
Onore, C. E., Schwartzer, J. J., Careaga, M., Berman, R. F., & Ashwood, P. (2014) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2014.02.007 · Cited by 106 · see citing works
GM‐CSF promotes migration of human monocytes across the blood brain barrier
Vogel, D. Y. S., Kooij, G., Heijnen, P. D. A. M., Breur, M., Peferoen, L. A. N., van der Valk, P., de Vries, H. E., Amor, S., & Dijkstra, C. D. (2015) · European Journal of Immunology · doi:10.1002/eji.201444960 · Cited by 94 · see citing works
Inflammatory macrophage phenotype in BTBR T+tf/J mice
Onore, C. E., Careaga, M., Babineau, B. A., Schwartzer, J. J., Berman, R. F., & Ashwood, P. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2013.00158 · Cited by 77 · see citing works
MLean, N. A., & Verge, V. M. K. (2016) · Glia · doi:10.1002/glia.23021 · Cited by 62 · see citing works
miR-124: A Promising Therapeutic Target for Central Nervous System Injuries and Diseases
Xu, J., Zheng, Y., Wang, L., Liu, Y., Wang, X., Li, Y., & Chi, G. (2022) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-021-01091-6 · Cited by 55 · see citing works
- Authors
- Mikita, J., Dubourdieu-Cassagno, N., Deloire, M. S., Vekris, A., Biran, M., Raffard, G., Brochet, B., Canron, M.-H., Franconi, J.-M., Boiziau, C., & Petry, K. G.
- Affiliations
- Université Bordeaux Segalen (FR)
- University Victor Segalen, France.
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Boiziau, Claudine
- Venue
- Multiple Sclerosis Journal
- Publisher
- SAGE Publications
- Published
- 2010-09-02
- Volume
- 17
- Issue
- 1
- Pages
- 2-15
- ISSN
- 1352-4585 (ISSN-L)
- 1477-0970
- OpenAlex
- W2142808413
- Cited by
- 358
- References
- 7
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 8 · 2023: 11 · 2022: 23 · 2021: 18 · 2020: 21 · 2019: 28 · 2018: 28 · 2017: 28 · 2016: 36 · 2015: 37 · 2014: 45 · 2013: 27 · 2012: 25
- FWCI
- 14.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Multiple Sclerosis Journal (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- multiple sclerosis, experimental autoimmune encephalomyelitis, macrophage polarization, monocytes, relapse, neuroinflammation, microglia, macrophage tracking, immunomodulation, cell therapy, disease-modifying therapy
- MeSH terms
- Animals, Brain, Cells, Cultured, Contrast Media, Dextrans, Encephalomyelitis, Autoimmune, Experimental, Female, Macrophage Activation, Macrophages, Magnetic Resonance Imaging, Monocytes, Multiple Sclerosis, Severity of Illness Index, Time Factors, Rats, Nitric Oxide Synthase Type II, Magnetite Nanoparticles
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